Thrombospondin 2 is a tumor stemness protein marker based on the cluster analysis combined with immune infiltration in gastric cancer.

Platelet reactive protein 2 (PRP2) is closely related to the characteristics of tumor stem cells. Its role in cancer development and metastasis has received increasing attention, especially its interaction with the immune microenvironment. The study used cluster analysis to extract expression data of multiple cancer types from public databases, and combined with immune infiltration analysis, to evaluate the expression level of PRP2 and its correlation with different immune cell infiltration. Bioinformatics tools were used to analyze the correlation between PRP2 and tumor stem cell markers. The results show that PRP2 is significantly upregulated in a variety of cancers and is closely related to tumor stem cell characteristics. Immunoinfiltration analysis showed that the high expression of PRP2 was associated with a significant increase in immunosuppression-related cell infiltration. Through cluster analysis, we identified the expression pattern of PRP2 in different cancer types, indicating that it may be used as a biomarker for early diagnosis and prognosis assessment, and its expression is closely related to the immune microenvironment, indicating its important role in cancer biology and potential application value in the tumor immune microenvironment.

Simple Sitting Baduanjin mind-body exercise: randomized controlled trial protocol for advanced cancer patients with the fatigue-sleep disturbance symptom cluster.

BACKGROUND: Advanced cancer patients commonly suffer from a fatigue-sleep disturbance symptom cluster. Baduanjin is considered a promising mind-body exercise for relieving the fatigue-sleep disturbance symptom cluster. However, few studies have investigated a tailored Baduanjin for advanced cancer patients. The proposed study will create an optimized Baduanjin exercise program to adapt to advanced cancer patients and evaluate the effect of a Simple Sitting Baduanjin (SSBDJ) mind-body exercise on the fatigue-sleep disturbance symptom cluster among advanced cancer patients. METHODS: The study will be a prospective, assessor-blinded, two-arm, randomized controlled trial, involving a 12-week intervention and 4-week follow-up. A total of 108 advanced cancer patients experiencing the fatigue-sleep disturbance symptom cluster will be recruited from two tertiary general hospitals in China. Participants will be randomized to an experimental group (n = 54) or a control group (n = 54). The experimental group will receive a 12-week SSBDJ intervention plus the usual care, and the control group will receive only the usual care. Outcomes including fatigue-sleep disturbance symptom cluster, fatigue, sleep disturbance, and quality of life will be measured before the intervention, at the 4th, 8th, and 12th weeks of the intervention, and 4 weeks after the intervention. The intention-to-treat principle and a generalized estimating equation will be used to analyze data. DISCUSSION: This study may produce a new Baduanjin exercise prescription that is user-friendly, simple to execute, more targeted, and adaptable. If proven effective, this approach may be integrated into routine cancer care to manage the fatigue-sleep disturbance symptom cluster and improve QOL in advanced cancer patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-2,300,072,331. Registered on 9 June 2023.

All-aqueous synthesis of alginate complexed with fibrillated protein microcapsules for membrane-bounded culture of tumor spheroids.

Water-in-water (W/W) emulsions provide bio-compatible all-aqueous compartments for artificial patterning and assembly of living cells. Successful entrapment of cells within a W/W emulsion via the formation of semipermeable capsules is a prerequisite for regulating on the size, shape, and architecture of cell aggregates. However, the high permeability and instability of the W/W interface, restricting the assembly of stable capsules, pose a fundamental challenge for cell entrapment. The current study addresses this problem by synthesizing multi-armed protein fibrils and controlling their assembly at the W/W interface. The multi-armed protein fibrils, also known as 'fibril clusters', were prepared by cross-linking lysozyme fibrils with multi-arm polyethylene glycol (PEG) via click chemistry. Compared to linear-structured fibrils, fibril clusters are strongly adsorbed at the W/W interface, forming an interconnected meshwork that better stabilizes the W/W emulsion. Moreover, when fibril clusters are complexed with alginate, the hybrid microcapsules demonstrate excellent mechanical robustness, semi-permeability, cytocompatibility and biodegradability. These advantages enable the encapsulation, entrapment and long-term culture of tumor spheroids, with great promise for applications for anti-cancer drug screening, tumor disease modeling, and tissue repair engineering.

Clinical application of cluster analysis in patients with newly diagnosed type 2 diabetes.

AIMS: Early prevention and treatment of type 2 diabetes mellitus (T2DM) is still a huge challenge for patients and clinicians. Recently, a novel cluster-based diabetes classification was proposed which may offer the possibility to solve this problem. In this study, we report our performance of cluster analysis of individuals newly diagnosed with T2DM, our exploration of each subtype's clinical characteristics and medication treatment, and the comparison carried out concerning the risk for diabetes complications and comorbidities among subtypes by adjusting for influencing factors. We hope to promote the further application of cluster analysis in individuals with early-stage T2DM. METHODS: In this study, a k-means cluster algorithm was applied based on five indicators, namely, age, body mass index (BMI), glycosylated hemoglobin (HbA1c), homeostasis model assessment-2 insulin resistance (HOMA2-IR), and homeostasis model assessment-2 ß-cell function (HOMA2-ß), in order to perform the cluster analysis among 567 newly diagnosed participants with T2DM. The clinical characteristics and medication of each subtype were analyzed. The risk for diabetes complications and comorbidities in each subtype was compared by logistic regression analysis. RESULTS: The 567 patients were clustered into four subtypes, as follows: severe insulin-deficient diabetes (SIDD, 24.46%), age-related diabetes (MARD, 30.86%), mild obesity-related diabetes (MOD, 25.57%), and severe insulin-resistant diabetes (SIRD, 20.11%). According to the results of the oral glucose tolerance test (OGTT) and biochemical indices, fasting blood glucose (FBG), 2-hour postprandial blood glucose (2hBG), HbA1c, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglyceride-glucose index (TyG) were higher in SIDD and SIRD than in MARD and MOD. MOD had the highest fasting C-peptide (FCP), 2-hour postprandial C-peptide (2hCP), fasting insulin (FINS), 2-hour postprandial insulin (2hINS), serum creatinine (SCr), and uric acid (UA), while SIRD had the highest triglycerides (TGs) and TyG-BMI. Albumin transaminase (ALT) and albumin transaminase (AST) were higher in MOD and SIRD. As concerms medications, compared to the other subtypes, SIDD had a lower rate of metformin use (39.1%) and a higher rate of α-glucosidase inhibitor (AGI, 61.7%) and insulin (74.4%) use. SIRD showed the highest frequency of use of sodium-glucose cotransporter-2 inhibitors (SGLT-2i, 36.0%) and glucagon-like peptide-1 receptor agonists (GLP-1RA, 19.3%). Concerning diabetic complications and comorbidities, the prevalence of diabetic kidney disease (DKD), cardiovascular disease (CVD), non-alcoholic fatty liver disease (NAFLD), dyslipidemia, and hypertension differed significantly among subtypes. Employing logistic regression analysis, after adjusting for unmodifiable (sex and age) and modifiable related influences (e.g., BMI, HbA1c, and smoking), it was found that SIRD had the highest risk of developing DKD (odds ratio, OR = 2.001, 95% confidence interval (CI): 1.125-3.559) and dyslipidemia (OR = 3.550, 95% CI: 1.534-8.215). MOD was more likely to suffer from NAFLD (OR = 3.301, 95%CI: 1.586-6.870). CONCLUSIONS: Patients with newly diagnosed T2DM can be successfully clustered into four subtypes with different clinical characteristics, medication treatment, and risks for diabetes-related complications and comorbidities, the cluster-based diabetes classification possibly being beneficial both for prevention of secondary diabetes and for establishment of a theoretical basis for precision medicine.

Assessing Gender Differences for Non-Predictable Breakthrough Cancer Pain Phenomenon: A Secondary Analysis from IOPS-MS Study.

Purpose: Breakthrough cancer pain (BTcP) is a temporary exacerbation of pain that "breaks through" a phase of adequate pain control by an opioid-based therapy. The non-predictable BTcP (NP-BTcP) subtype occurs in the absence of any specific activity. Evidence showed that gender differences exist in pain response sensitivity and clinical pain risk. This analysis aimed to signify the gender differences for the NP-BTcP phenomenon. Patients and Methods: This is a secondary analysis of the Italian Oncologic Pain multiSetting-Multicentric Survey (IOPS-MS), the largest study on BTcP. The subset of NP-BTcP cases for non-gender-specific cancer was considered. Univariable and multivariate analyses were conducted to identify gender differences for the NP-BTcP profile about its intensity, number of episodes per day, and type. A metastatic status-stratified analysis was performed to compare gender with the main clinical variables among the population with NP-BTcP. Results: Males exhibited a higher occurrence of BTcP in the thorax region compared to females (15% vs 11%, respectively, p = 0.03). Males also had a higher onset of BTcP, a higher BTcP therapy dosage (33% vs 28%, p = 0.04, mean: 201 vs 186, p = 0.02) and a lower Karnofsky score (mean: 46.9 vs 49.2, p = 0.03) compared to females. Similar gender differences were found for metastatic patients in the BTcP site (14% vs 8.5%, respectively; p = 0.01), peak onset (33% vs 27%, p = 0.02), BTcP therapy dosage (199 vs 185, p=0.04), and Karnofsky score (mean 47.5 vs 50.4, p = 0.009). Phenotype 2 was more characterized by non-metastatic males (41% vs 23%, p = 0.020) while non-metastatic females presence was predominant among others. Conclusion: In this study, gender differences according to site, onset and dosage of BTcP were found. The phenotype characterization of BTcP needs to be further investigated for a possible useful function in the management of cancer-related pain in non-metastatic patients.

[Multimorbidity as a predictor for inpatient admission in clinical emergency and acute medicine : Single-center cluster analysis]. / Multimorbidität als Prädiktor für eine stationäre Aufnahme in der klinischen Notfall- und Akutmedizin : Monozentrische Clusteranalyse.

BACKGROUND: Parallel to demographic trends, an increase of multimorbid patients in emergency and acute medicine is prominent. To define easily applicable criteria for the necessity of inpatient admission, a hierarchical cluster analysis was performed. METHODS: In a retrospective, single-center study data of n = 35,249 emergency cases (01/2016-05/2018) were statistically analyzed. Multimorbidity (MM) was defined by at least five ICD-10-GM diagnoses resulting from treatment. A hierarchical cluster analysis was performed for those diagnoses initially summarized into 112 diagnosis subclusters to determine specific clusters of in- and outpatient cases. RESULTS: Hospital admission was determined in 81.2% of all ED patients (n = 28,633); 54.7% of inpatients (n = 15,652) and 0.97% of outpatient cases (n = 64) met the criteria for multimorbidity and the age difference between them was highly significant (68.7/60.8 years; p < 0.001). Using a hierarchical cluster analysis, 13 clusters with different diagnoses were identified for inpatient multimorbid patients (MP) and 7 clusters with primarily hematological malignancies for outpatient MP. The length of stay in the ED of inpatient MP was more than twice as long (max. 8.3 h) as for outpatient MP (max. 3.2 h.). CONCLUSIONS: The combination of diagnoses typical for MM were characterized as clusters in this study. In contrast to single or combined single diagnoses, the statistically determined characterization of clusters allows for a significantly more accurate prediction of ED patients' disposition as well as for economic process allocation.

Mitochondrial acyl carrier protein, Acp1, required for iron-sulfur cluster assembly in mitochondria and cytoplasm in Saccharomyces cerevisiae.

Mitochondria perform vital biosynthetic processes, including fatty acid synthesis and iron-sulfur (FeS) cluster biogenesis. In Saccharomyces cerevisiae mitochondria, the acyl carrier protein Acp1 participates in type II fatty acid synthesis, requiring a 4-phosphopantetheine (PP) prosthetic group. Acp1 also interacts with the mitochondrial FeS cluster assembly complex that contains the cysteine desulfurase Nfs1. Here we investigated the role of Acp1 in FeS cluster biogenesis in mitochondria and cytoplasm. In the Acp1-depleted (Acp1↓) cells, biogenesis of mitochondrial FeS proteins was impaired, likely due to greatly reduced Nfs1 protein and/or its persulfide-forming activity. Formation of cytoplasmic FeS proteins was also deficient, suggesting a disruption in generating the (Fe-S)int intermediate, that is exported from mitochondria and is subsequently utilized for cytoplasmic FeS cluster assembly. Iron homeostasis was perturbed, with enhanced iron uptake into the cells and accumulation of iron in mitochondria. The Δppt2 strain, lacking the mitochondrial ability to add PP to Acp1, phenocopied the Acp1↓ cells. These data suggest that the holo form of Acp1 with the PP-conjugated acyl chain is required for stability of the Nfs1 protein and/or stimulation of its persulfide-forming activity. Thus, mitochondria lacking Acp1 (or Ppt2) cannot support FeS cluster biogenesis in mitochondria or cytoplasm, leading to disrupted iron homeostasis.

Profiling iNPH features through cluster analysis: an aid for clinical suspicion and diagnosis.

PURPOSE: Idiopathic Normal Pressure Hydrocephalus (iNPH) is a neurological syndrome defined by gait disturbance, cognitive impairment and urinary incontinence. However, its clinical presentation can vary widely due to overlapping syndromes and common comorbidities in older adults. This study aims to provide practical guidance to aid in the clinical suspicion and support the diagnostic and therapeutic processes for these patients. METHODS: Six quantitative variables regarding clinical, functional, and demographic aspects were considered for a large sample of patients with diagnosed iNPH. Principal component analysis (PCA) was adopted to define the main dimensions explaining the variability of the phenomenon. Then, two clusters of iNPH patients were described. RESULTS: 178 patients were included in the analysis. The PCA produced two dimensions covering 61.8% of the total variability. The first one relied mainly on both clinical (mRS, iNPHGs) and functional (TUG, Tinetti) variables, while the second one was represented mainly on the demographic pattern (age and education). Cluster analysis depicted two main groups of patients. Cluster n.1 is composed of individuals who are older, more disabled, with poor functional performances, and highly symptomatic. Cluster n.2 patients are slightly younger, more educated, fitter, and with more nuanced clinical aspects. CONCLUSIONS: Profiling iNPH patients using quantitative variables and cluster analysis can help identify distinct characteristics of these patients, aiding in the guidance of both medical and surgical interventions.

RUNX1::MIR99AHG Chimera in Acute Myeloid Leukemia.

RUNX1 fuses with over 70 different partner genes in hematological neoplasms. While common RUNX1 chimeras have been extensively studied and their prognosis is well established, our current understanding of less common RUNX1 chimeras is limited. Here, we present a case of acute myeloid leukemia (AML) with a rare RUNX1 chimera. Bone marrow cells obtained at diagnosis from a 71-year-old patient diagnosed with AML-M5 were studied using G-banding, fluorescence in situ hybridization, array comparative genomic hybridization, RNA sequencing, PCR, and Sanger sequencing. Combined findings from the abovementioned assays suggested three cytogenetic clones: one with a normal karyotype, one with inv(21)(q21q22), and one with two inv(21)(q21q22). The molecular analysis revealed the fusion of RUNX1 with MIR99AHG (at 21q21.1), further supporting the presence of an inv(21)(q21q22). The present case is the third reported AML harboring a RUNX1::MIR99AHG chimera. Similar to the two previously described AML patients, our case also had an FLT3 aberration.

Downregulation of Iron-Sulfur Cluster Biogenesis May Contribute to Hyperglycemia-Mediated Diabetic Peripheral Neuropathy in Murine Models.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is considered one of the most common chronic complications of diabetes. Impairment of mitochondrial function is regarded as one of the causes. Iron-sulfur clusters are essential cofactors for numerous iron-sulfur (Fe-S)-containing proteins/enzymes, including mitochondrial electron transport chain complex I, II, and III and aconitase. METHODS: To determine the impact of hyperglycemia on peripheral nerves, we used Schwann-like RSC96 cells and classical db/db mice to detect the expression of Fe-S-related proteins, mitochondrially enzymatic activities, and iron metabolism. Subsequently, we treated high-glucose-induced RSC96 cells and db/db mice with pioglitazone (PGZ), respectively, to evaluate the effects on Fe-S cluster biogenesis, mitochondrial function, and animal behavior. RESULTS: We found that the core components of Fe-S biogenesis machinery, such as frataxin (Fxn) and scaffold protein IscU, significantly decreased in high-glucose-induced RSC96 cells and db/db mice, accompanied by compromised mitochondrial Fe-S-containing enzymatic activities, such as complex I and II and aconitase. Consequently, oxidative stress and inflammation increased. PGZ not only has antidiabetic effects but also increases the expression of Fxn and IscU to enhance mitochondrial function in RSC96 cells and db/db mice. Meanwhile, PGZ significantly alleviated sciatic nerve injury and improved peripheral neuronal behavior, accompanied by suppressed oxidative stress and inflammation in the sciatic nerve of the db/db mice. CONCLUSIONS: Iron-sulfur cluster deficiency may contribute to hyperglycemia-mediated DPN.

Near-infrared and ultrasound triggered Pt/Pd-engineered cluster bombs for the treatment of solid tumors.

Owing to the dense extracellular matrix and high interstitial fluid pressure in the tumor microenvironment, methods which enhance the permeation and retention of nano drugs into liver tumors remain unsatisfactory for successful tumor treatment. We designed a near-infrared (NIR)- and ultrasound (US)-triggered Pt/Pd-engineered "cluster bomb" (Pt/Pd-CB) which actively penetrates liver cancer cell membranes and achieves photothermal and sonodynamic therapy (SDT). The physical forces generated by the fast expansion and collapse of perfluoropentane nanodroplets eject "sub bombs" (Pt/Pd nanoalloys) into liver cancer cells upon activation by NIR and US. Pt/Pd nanoalloys can then convert H2O2 into O2 to alleviate hypoxia and boost SDT efficiency while exhibiting a highly efficient photothermal response under NIR irradiation. Our findings might especially be promising for the treatment of solid tumors.

Identifying heterogeneous subgroups of systemic autoimmune diseases by applying a joint dimension reduction and clustering approach to immunomarkers.

BACKGROUND: The high complexity of systemic autoimmune diseases (SADs) has hindered precise management. This study aims to investigate heterogeneity in SADs. METHODS: We applied a joint cluster analysis, which jointed multiple correspondence analysis and k-means, to immunomarkers and measured the heterogeneity of clusters by examining differences in immunomarkers and clinical manifestations. The electronic health records of patients who received an antinuclear antibody test and were diagnosed with SADs, namely systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and Sjögren's syndrome (SS), were retrieved between 2001 and 2016 from hospitals in Taiwan. RESULTS: With distinctive patterns of immunomarkers, a total of 11,923 patients with the three SADs were grouped into six clusters. None of the clusters was composed only of a single SAD, and these clusters demonstrated considerable differences in clinical manifestation. Both patients with SLE and SS had a more dispersed distribution in the six clusters. Among patients with SLE, the occurrence of renal compromise was higher in Clusters 3 and 6 (52% and 51%) than in the other clusters (p < 0.001). Cluster 3 also had a high proportion of patients with discoid lupus (60%) than did Cluster 6 (39%; p < 0.001). Patients with SS in Cluster 3 were the most distinctive because of the high occurrence of immunity disorders (63%) and other and unspecified benign neoplasm (58%) with statistical significance compared with the other clusters (all p < 0.05). CONCLUSIONS: The immunomarker-driven clustering method could recognise more clinically relevant subgroups of the SADs and would provide a more precise diagnosis basis.

Considerations for Using Neuroblastoma Cell Lines to Examine the Roles of Iron and Ferroptosis in Neurodegeneration.

Ferroptosis is an iron-dependent form of programmed cell death that is influenced by biological processes such as iron metabolism and senescence. As brain iron levels increase with aging, ferroptosis is also implicated in the development of age-related pathologic conditions such as Alzheimer's disease (AD) and related dementias (ADRD). Indeed, inhibitors of ferroptosis have been shown to be protective in models of degenerative brain disorders like AD/ADRD. Given the inaccessibility of the living human brain for metabolic studies, the goal of this work was to characterize an in vitro model for understanding how aging and iron availability influence neuronal iron metabolism and ferroptosis. First, the human (SH-SY5Y) and mouse (Neuro-2a) neuroblastoma lines were terminally differentiated into mature neurons by culturing in all-trans-retinoic acid for at least 72 h. Despite demonstrating all signs of neuronal differentiation and maturation, including increased expression of the iron storage protein ferritin, we discovered that differentiation conferred ferroptosis resistance in both cell lines. Gene expression data indicates differentiated neurons increase their capacity to protect against iron-mediated oxidative damage by augmenting cystine import, and subsequently increasing intracellular cysteine levels, to promote glutathione production and glutathione peroxidase activity (GPX). In support of this hypothesis, we found that culturing differentiated neurons in cysteine-depleted media sensitized them to GPX4 inhibition, and that these effects are mitigated by cystine supplementation. Such findings are important as they provide guidance for the use of in vitro experimental models to investigate the role of ferroptosis in neurodegeneration in pathologies such as ADRD.

Cluster of Differentiation Markers and Human Leukocyte Antigen Expression in Chronic Lymphocytic Leukemia Patients: Correlations and Clinical Relevance.

Chronic lymphocytic leukemia (CLL) is a distinct category of lymphoproliferative disorder characterized by the clonal expansion of mature B cells, followed by their accumulation in primary and secondary lymphoid organs. Cluster of differentiation (CD) markers such as CD79b, CD45, CD23, CD22 and CD81 serve as reliable prognostic indicators in CLL as well as the human leukocyte antigen (HLA) with its well-documented associations with various cancers. This study aims to investigate, for the first time, potential connections between HLA typing and CD marker expression in CLL. Although it is one of the most prevalent neoplasms, there is a need for biomarkers that can improve survival. This study included 66 CLL patients and 100 controls, with all samples analyzed using biochemical methods, flow cytometry, and cytomorphology. Next-generation sequencing was performed for HLA typing. The results indicate that several CD markers are statistically associated with different HLA alleles, specifically CD45 with HLA-C*07:01:01; CD79b with HLA-DPA1*02:01:02; CD23 with HLA-B*39:01:01; CD22 with HLA-B*49:01:01, HLA-C*07:01:01, HLA-DPB1*02:01:02, and HLA-DRB1*07:01:01; and CD81 with HLA-DPB1*04:02:01, HLA-DQA1*01:04:01, and HLA-DQB1*05:03:01. In conclusion, this research demonstrates significant statistical links between HLA genes and immunophenotypic markers in CLL patients, shedding new light on the immunological context of CLL.

Regulation of Safracin Biosynthesis and Transport in Pseudomonas poae PMA22.

Pseudomonas poae PMA22 produces safracins, a family of compounds with potent broad-spectrum anti-bacterial and anti-tumor activities. The safracins' biosynthetic gene cluster (BGC sac) consists of 11 ORFs organized in two divergent operons (sacABCDEFGHK and sacIJ) that are controlled by Pa and Pi promoters. Contiguous to the BGC sac, we have located a gene that encodes a putative global regulator of the LysR family annotated as MexT that was originally described as a transcriptional activator of the MexEF-OprN multidrug efflux pump in Pseudomonas. Through both in vitro and in vivo experiments, we have demonstrated the involvement of the dual regulatory system MexT-MexS on the BGC sac expression acting as an activator and a repressor, respectively. The MexEF-OprN transport system of PMA22, also controlled by MexT, was shown to play a fundamental role in the metabolism of safracin. The overexpression of mexEF-oprN in PMA22 resulted in fourfold higher production levels of safracin. These results illustrate how a pleiotropic regulatory system can be critical to optimizing the production of tailored secondary metabolites, not only through direct interaction with the BGC promoters, but also by controlling their transport.

Multi-Cluster Approaches to Radio Sensor Array Channel Modeling and Simulation.

In this paper, we explore the physical propagation environment of radio waves by describing it in terms of distant scattering clusters. Each cluster consists of numerous scattering objects that may exhibit certain statistical properties. By utilizing geometry-based methods, we can study the channel second-order statistics (CSOS), where each distant scattering cluster corresponds to a CSOS, contributes a portion to the Doppler spectrum, and is associated with a state-space multiple-input and multiple-output (MIMO) radio channel model. Consequently, the physical propagation environment of radio waves can be modeled by summing multiple state-space MIMO radio channel models. This approach offers three key advantages: simplicity, the ability to construct the entire Doppler power spectrum from multiple uncorrelated distant scattering clusters, and the capability to obtain the channels contributed by these clusters by summing the individual channels. This methodology enables the reconstruction of the radio wave propagation environment in a simulated manner and is crucial for developing massive MIMO channel models.

Nanodosimetric investigation of the track structure of therapeutic carbon ion radiation part 1: measurement of ionization cluster size distributions.

At the Heidelberg Ion-Beam Therapy Center, the track structure of carbon ions of therapeutic energy after penetrating layers of simulated tissue was investigated for the first time. Measurements were conducted with carbon ion beams of different energies and polymethyl methacrylate (PMMA) absorbers of different thicknesses to realize different depths in the phantom along the pristine Bragg peak. Ionization cluster size (ICS) distributions resulting from the mixed radiation field behind the PMMA absorbers were measured using an ion-counting nanodosimeter. Two different measurements were carried out: (i) variation of the PMMA absorber thickness with constant carbon ion beam energy and (ii) combined variation of PMMA absorber thickness and carbon ion beam energy such that the kinetic energy of the carbon ions in the target volume is constant. The data analysis revealed unexpectedly high mean ICS values compared to stopping power calculations and the data measured at lower energies in earlier work. This suggests that in the measurements the carbon ion kinetic energies behind the PMMA absorber may have deviated considerably from the expected values obtained by the calculations. In addition, the results indicate the presence of a marked contribution of nuclear fragments to the measured ICS distributions, especially if the carbon ion does not cross the target volume.

ActO, a positive cluster-situated regulator for actinomycins biosynthesis in Streptomyces antibioticus ZS.

Actinomycins are a class of cyclic lipopeptide antibiotics produced by Streptomyces, which have rich biological activities and demonstrate great potential value. Among them, actinomycin D is currently the effective drug for some malignant tumor diseases. Although the chemical properties, biological activities and biosynthesis of actinomycins have been extensively studied, the regulation of their biosynthesis remains poorly understood. Streptomyces antibioticus ZS isolated from deep-sea corals is a producer of actinomycin D and actinomycin V. Here, we reported the characterization of a cluster-situated regulator ActO in actinomycins biosynthetic gene cluster (act cluster) of S. antibioticus ZS, which belongs to LmbU family. Deletion of actO completely blocked the synthesis of actinomycins. Overexpression of actO increased the yields of actinomycin D and actinomycin V by 4.4 fold and 2.6 fold, respectively. The result of RT-qPCR showed that ActO activates the transcription of all genes in act cluster. However, no specific binding of His6-ActO to the promoters of target genes was observed after electrophoretic mobility shift assay (EMSA). These results proved that ActO serves as a positive regulator involved in the biosynthesis of actinomycins, affecting the transcription of all genes related to the synthesis of intermediates, skeleton modification and extracellular transportation of final products. Moreover, we demonstrated that overexpression of actO is a novel strategy to increase the yields of actinomycins.

Simulating the Effect of Removing Circulating Tumor Cells (CTCs) from Blood Reveals That Only Implantable Devices Can Significantly Reduce Metastatic Burden of Patients.

Circulating tumor cells (CTCs) are cells that have separated from a solid cancerous lesion and entered the bloodstream. They play a crucial role in driving the metastatic spread to distant organs, which is the leading cause of cancer-related deaths. Various concepts for blood purification devices aiming to remove CTCs from the blood and prevent metastases have been developed. Until now, it is not clear if such devices can indeed reduce new metastasis formation in a significant way. Here, we present a simple theoretical model of CTCs in the bloodstream that can be used to predict a reduction in metastatic burden using an extracorporeal or intracorporeal blood purification device. The model consists of a system of ordinary differential equations that was numerically solved and simulated. Various simulations with different parameter settings of extracorporeal and intracorporeal devices revealed that only devices implanted directly in tumor-draining vessels can reduce the metastatic burden significantly. Even if an extracorporeal device is used permanently, the reduction in metastases is only 82%, while a permanently operating implanted device in the tumor-draining vessel would achieve a reduction of 99.8%. These results are mainly due to the fact that only a small fraction of CTCs reaches peripheral circulation, resulting in a proportionally small amount of purified blood in extracorporeal devices.

Symptom clusters of patients with advanced thyroid cancer: a cross-sectional study.

PURPOSE: To investigate and analyze the symptom clusters of patients with advanced thyroid cancer and provide a basis for developing targeted symptom management measures. METHODS: Patients who visited a multidisciplinary outpatient service for advanced thyroid cancer at a tertiary A hospital in Sichuan Province from April 2022 to April 2023 were selected using convenience sampling. A cross-sectional survey was conducted using the M.D. Anderson Symptom Inventory-Thyroid Cancer module (MDASI-THY). Symptom clusters were extracted by exploratory factor analysis. RESULTS: Disturbed sleep had the highest incidence (75.7%) and severity (3.0 points), while mood distress had the highest incidence (63.5%) and severity (2.0 points) of symptom interference. Three symptom clusters were identified: mood-fatigue-sleep, digestive tract-sensation, and thyroid cancer-specific symptom clusters. CONCLUSION: Patients with advanced thyroid cancer have multiple symptom clusters that seriously affect their daily lives. Health care professionals should conduct targeted observation and preventive treatment to reduce the burden of symptoms on patients.